DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1 and 5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by GOTO (GOTO et al., WO 2021192861 A1, 2021-09-30, IDS).
The reference GOTO teaches “Hydrophobic ionic liquids exhibit high compatibility with hydrophobic solvents, oily substrates, and hydrophobic drugs, and can therefore be easily mixed with them. Furthermore, ionic liquids have high permeability to the permeability barrier of the stratum corneum, allowing for easy transdermal absorption. Therefore, hydrophobic ionic liquids can be particularly utilized in transdermal drug delivery systems (DDS)”[0057] and “As a result of diligent research to solve the above problems, the inventors have found that by combining fatty acids and phospholipids having cationic groups to construct an ionic liquid, it is possible to realize an ionic liquid that has low toxicity and high solubility in both hydrophilic and hydrophobic substances”[0007]. The reference GOTO teaches “The lipid matrix structure (lamellar cholesterol, fatty acids, and ceramides) and the keratinous protein structure of the stratum corneum are major barriers to transdermal drug delivery systems (DDS) and affect the rate of drug diffusion into the deeper layers of the skin… The breakdown of the stratum corneum is directly related to the molecular diffusion of drugs passing through the skin. The deformability of the α-helix colloid and β-sheet structures of keratinous proteins is enhanced, improving drug penetration. These shifts were facilitated in ionic liquids by the lipid-soluble cations and fatty acid anions in the ionic liquids”[0109].
The reference GOTO teaches the following ionic liquid for transdermal drug delivery[0054]. Wherein the carboxylate ions are selected from linoleic acid, oleic acid, acetic acid, or stearic acid[0053-0054].
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This anticipates claim 1 as one of ordinary skill in the art would at once envisage the oleic acid with the cation for use with a low permeability drug.
The reference GOTO teaches “Furthermore, the form of the formulation according to this embodiment is not particularly limited and may be any form, such as an oral drug, a topical drug, or an injectable drug”[0062]. This anticipates claim 5.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-2, 5, 6-9, 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over QUAY (QUAY et al., US20040028613A1, 2004-02-12, IDS) in view of GOTO (GOTO et al., WO 2021192861 A1, 2021-09-30, IDS).
The reference QUAY teaches “Various methods and formulations have been attempted to enhance the absorption of drugs across mucosal surfaces. Penetration enhancing substances that facilitate the transport of solutes across biological membranes are widely reported in the art for facilitating mucosal drug delivery (See, e.g., Lee et al., 8 Critical Reviews in Therapeutic Drug Carrier Systems 91, 1991). Mucosal penetration enhancers represented in these reports include (a) chelators (e.g., EDTA, citric acid, salicylates), (b) surfactants (e.g., sodium dodecyl sulfate (SDS)), (c) non-surfactants (e.g., unsaturated cyclic ureas), (d) bile salts (e.g., sodium deoxycholate, sodium taurocholate), and (e) fatty acids (e.g., oleic acid, acylcarnitines, mono- and diglycerides). Numerous additional agents and mechanisms have been proposed for enhancing mucosal penetration of drugs”[0006] and “Like liposomes, unsaturated long chain fatty acids, which also have enhancing activity for mucosal absorption, can form closed vesicles with bilayer-like structures (so called "ufasomes"). These can be formed, for example, using oleic acid to entrap dopamine receptor agonists, as well as biologically active peptides and proteins, for mucosal delivery within the invention”[0397].
The reference QUAY teaches “More simplified delivery systems for use within the invention include the use of cationic lipids as delivery vehicles or carriers, which can be effectively employed to provide an electrostatic interaction between the lipid carrier and such charged biologically active agents (see, e.g., Hope et al., Molecular Membrane Biology 15:1-14, 1998, incorporated herein by reference). This allows efficient packaging of the drugs into a form suitable for mucosal administration and delivery to systemic compartments... Exemplary delivery vehicles of this type for use within the invention include cationic lipids (e.g., N-(2,3-(dioleyloxy)propyl)-N,N,N-trimethyl am-monium chloride (DOTMA)), quarternary ammonium salts (e.g., N,N-dioleyl-N, N-dimethylammonium chloride (DODAC)), cationic derivatives of cholesterol (e.g., 3[beta](N-(N',N-dimethylaminoethane-carbamoyl-cholesterol (DC-chol)), and lipids characterized by multivalent headgroups (e.g., dioctadecyldimethylammonium chloride (DOGS), commercially available as Transfectam(R))”[0399].
This helps to teach claims 1-2, 9.
The reference QUAY teaches “The enhanced delivery methods and compositions of the invention provide for therapeutically effective mucosal delivery of dopamine receptor agonists for prevention or treatment of a variety of disease and conditions in mammalian subjects. The dopamine receptor agonist can be administered via a variety of mucosal routes, for example by contacting to dopamine receptor agonist to a nasal mucosal epithelium, a bronchial or pulmonary mucosal epithelium, an oral, gastric, intestinal or rectal mucosal epithelium, or a vaginal mucosal epithelium”[0028].
This helps to teach claims 5, 8, 11.
The reference QUAY does not teach the combination of the anionic oleic acid with the cationic lipid (all claims) with or without the drug.
The reference GOTO teaches “Hydrophobic ionic liquids exhibit high compatibility with hydrophobic solvents, oily substrates, and hydrophobic drugs, and can therefore be easily mixed with them. Furthermore, ionic liquids have high permeability to the permeability barrier of the stratum corneum, allowing for easy transdermal absorption. Therefore, hydrophobic ionic liquids can be particularly utilized in transdermal drug delivery systems (DDS)”[0057] and “As a result of diligent research to solve the above problems, the inventors have found that by combining fatty acids and phospholipids having cationic groups to construct an ionic liquid, it is possible to realize an ionic liquid that has low toxicity and high solubility in both hydrophilic and hydrophobic substances”[0007]. The reference GOTO teaches “The lipid matrix structure (lamellar cholesterol, fatty acids, and ceramides) and the keratinous protein structure of the stratum corneum are major barriers to transdermal drug delivery systems (DDS) and affect the rate of drug diffusion into the deeper layers of the skin… The breakdown of the stratum corneum is directly related to the molecular diffusion of drugs passing through the skin. The deformability of the α-helix colloid and β-sheet structures of keratinous proteins is enhanced, improving drug penetration. These shifts were facilitated in ionic liquids by the lipid-soluble cations and fatty acid anions in the ionic liquids”[0109].
The reference GOTO teaches the following ionic liquid for transdermal drug delivery[0054]. Wherein the carboxylate ions are selected from linoleic acid, oleic acid, acetic acid, or stearic acid[0053-0054].
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This helps to teach claims 1-2.
The reference GOTO teaches “Furthermore, the form of the formulation according to this embodiment is not particularly limited and may be any form, such as an oral drug, a topical drug, or an injectable drug”[0062]. This helps to teach claim 5.
The reference GOTO demonstrates implicitly by lack of claiming a drug with the reference composition (in the reference claims) that the composition of the ionic liquid was conceived to exist both by itself and in context with a drug. This helps to teach claims 6-7.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified QUAY with GOTO because QUAY teaches that oleic acid and cationic lipids (such as DOTMA) can be used for enhancing the absorption of drugs across mucosal surfaces and GOTO teaches oleic acid and cationic lipids can be combined for improved drug delivery enhancements. One would have a reasonable expectation of success because the cationic lipids and oleic acid are both known for the same purpose separately and because combining them had a beneficial outcome for other drug delivery systems. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). One would have motivation to do so to possibly improve delivery of drugs across mucosal surfaces.
Claim(s) 1-2, 4-5, 6-9, 11-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over QUAY (QUAY et al., US20040028613A1, 2004-02-12, IDS) in view of GOTO (GOTO et al., WO 2021192861 A1, 2021-09-30, IDS) further in view of Pei (Pei et al., Small molecule PROTACs: an emerging technology for targeted therapy in drug discovery, RSC Adv., 2019, 9, 16967).
The references QUAY and GOTO have been discussed supra and do not discuss when the drug is PROTAC(claims 4 and 12).
The reference Pei teaches “Curing malignant carcinomas is a grand ambition in the development of human health. Over the past decades, targeted therapies have become one of the most successful ways of achieving this. Of these approaches, small molecule inhibitors and monoclonal antibodies are two major methods, however several barriers to their development and clinical use still exist. The use of proteolysis-targeting chimeras (PROTACs) is a new technology through utilizing a intracellular ubiquitin-proteasome system to induce targeted protein degradation, is receiving much attention in the field of targeted therapies. Hetero bifunctional PROTACs have the potential to eliminate the “undruggable” proteome that comprises about 85% of human proteins, which indicates their great prospects in therapeutic fields. However, there are some hurdles preventing current PROTACs moving from bench to clinic, such as delivery and bioavailability. This review provides an overview of the development of PROTAC technology and will briefly summarize the future possible directions of this approach”(abstract).
This helps to teach claims 4 and 12.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified QUAY and GOTO with Pei because QUAY and GOTO both teach methods of improving drug delivery and Pei teaches a drug type (PROTAC) that has current hurdles that include issues with delivery and bioavailability. One would be motivated to improve the delivery and bioavailability of PROTAC molecules to overcome these current issues to help advance this drug type. One would have a reasonable expectation of success because GOTO teaches the use of ionic liquids for a wide range of drugs.
Claim(s) 1-3, 5, 6-9, 10-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over QUAY (QUAY et al., US20040028613A1, 2004-02-12, IDS) in view of GOTO (GOTO et al., WO 2021192861 A1, 2021-09-30, IDS) further in view of Mendonça (Mendonça et al., Advances in the Design of (Nano)Formulations for Delivery of Antisense Oligonucleotides and Small Interfering RNA: Focus on the Central Nervous System, Mol. Pharmaceutics 2021, 18, 1491−1506).
The references QUAY and GOTO have been discussed supra and do not discuss DODAP or DODMA (claims 3 and 10).
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The reference Mendonça teaches that DOTMA and DODAP or DODMA are all cationic lipids that have been used for the same purpose of lipid based nanoparticles (page 1497).
This helps to teach claims 3 and 10.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified QUAY and GOTO with Mendonça because both QUAY and GOTO teach cationic lipids, and QUAY teaches DOTMA as one possibility, and Mendonça teaches known alternatives for cationic lipids including DODAP and DODMA. One would have a motivation to substitute equivalents for the same purpose of being a cationic lipid to explore alternatives. One would have a reasonable expectation of success because they are known alternatives in the art.
Conclusion
Claims 1-12 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON AZAR HASTINGS whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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/A.A.H./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627
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